16-52450491-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001080430.4(TOX3):c.464G>A(p.Arg155Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000248 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
TOX3
NM_001080430.4 missense
NM_001080430.4 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 4.87
Genes affected
TOX3 (HGNC:11972): (TOX high mobility group box family member 3) The protein encoded by this gene contains an HMG-box, indicating that it may be involved in bending and unwinding of DNA and alteration of chromatin structure. The C-terminus of the encoded protein is glutamine-rich due to CAG repeats in the coding sequence. A minor allele of this gene has been implicated in an elevated risk of breast cancer. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1319904).
BS2
?
High AC in GnomAd at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TOX3 | NM_001080430.4 | c.464G>A | p.Arg155Gln | missense_variant | 4/7 | ENST00000219746.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TOX3 | ENST00000219746.14 | c.464G>A | p.Arg155Gln | missense_variant | 4/7 | 2 | NM_001080430.4 | A2 | |
TOX3 | ENST00000407228.7 | c.449G>A | p.Arg150Gln | missense_variant | 5/8 | 2 | P2 | ||
TOX3 | ENST00000563091.1 | c.356G>A | p.Arg119Gln | missense_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000197 AC: 30AN: 152182Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.000121 AC: 30AN: 248530Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 134878
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GnomAD4 exome AF: 0.000254 AC: 371AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.000239 AC XY: 174AN XY: 727132
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GnomAD4 genome ? AF: 0.000197 AC: 30AN: 152300Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74464
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | The c.464G>A (p.R155Q) alteration is located in exon 4 (coding exon 4) of the TOX3 gene. This alteration results from a G to A substitution at nucleotide position 464, causing the arginine (R) at amino acid position 155 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;.
Polyphen
0.97
.;D;.
Vest4
MVP
MPC
0.86
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at